ICAM1 antibody drug conjugates exert potent antitumor activity in papillary and anaplastic thyroid carcinoma

Peng Zhang; Changjuan Tao; Takaya Shimura; Andrew C Huang; Nana Kong; Yujie Dai; Shili Yao; Yun Xi; Xing Wang; Jianmin Fang; Marsha A Moses; Peng Guo

doi:10.1016/j.isci.2023.107272

ICAM1 antibody drug conjugates exert potent antitumor activity in papillary and anaplastic thyroid carcinoma

iScience. 2023 Jul 3;26(8):107272. doi: 10.1016/j.isci.2023.107272. eCollection 2023 Aug 18.

Authors

Peng Zhang^{1

2

3}, Changjuan Tao^{2

3

4}, Takaya Shimura⁵, Andrew C Huang⁶, Nana Kong⁶, Yujie Dai⁶, Shili Yao⁷, Yun Xi⁸, Xing Wang⁹, Jianmin Fang¹⁰, Marsha A Moses^{11

12}, Peng Guo³

Affiliations

¹ Department of Medical Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
² Key Laboratory of Head and Neck Cancer Translational Research of Zhejiang Province, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
³ Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
⁴ Department of Radiation Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
⁵ Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
⁶ MabPlex International, Yantai, Shandong 264006, China.
⁷ School of Materials Science and Engineering, Tianjin University, Tianjin 300072, China.
⁸ Department of Pathology, The Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
⁹ Department of Head and Neck Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
¹⁰ School of Life Science and Technology, Tongji University, Shanghai 200092, China.
¹¹ Vascular Biology Program, Boston Children's Hospital, Boston, MA 02115, USA.
¹² Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Abstract

Treatment options for anaplastic thyroid cancer (ATC) and refractory papillary thyroid carcinoma (PTC) are limited and outcomes remain poor. In this study, we determined via bioinformatic expression analyses and immunohistochemistry staining that intercellular adhesion molecule-1(ICAM1) is an attractive target for ATC and PTC. We designed and engineered two ICAM1-directed antibody-drug conjugate (I1-MMAE and I1-DXd), both of which potently and selectively ablate multiple human ATC and PTC cell lines without affecting non-plastic cells in vitro. Furthermore, I1-MMAE and I1-DXd mediated a potent tumor regression in ATC and PTC xenograft models. To develop a precision medicine, we also explored magnetic resonance imaging (MRI) as a non-invasive biomarker detection method to quantitatively map ICAM1 antigen expression in heterogeneous thyroid tumors. Taken together, this study provides a strong rationale for the further development of I1-MMAE and I1-DXd as promising therapeutic candidates to treat advanced PTC and ATC.

Keywords: Biological sciences; Cancer systems biology; Immunology; Natural sciences; Systems biology.